atacand dose range finding study in pediatric subjects 6 to <17 years of age

Conditions: Pediatric Hypertension

Summary: study 261a is a dose-ranging and safety study of candesartan cilexetil. it is a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group study with a 4 week treatment period in hypertensive pediatric subjects. subjects undergo a screening evaluation, then a 1-week, single-blind, placebo run-in after which eligible subjects are allocated to receive 1 of 3 dose levels of candesartan cilexetil or placebo. the study includes 2 panels based on subject weight. the primary efficacy analysis is based on the intent-to-treat population and tests for slope = 0 in a linear regression model with change in sitting systolic blood pressure as the dependent and non-zero dose pooled across weight panels as the independent variable. for subjects without a double-blind week 4 blood pressure determination, carrying the last value forward assigns the value. additional analyses will include data pooled from a similar dose ranging study conducted in children 1 to \< 6 years of age.


Eligibility criteria:
inclusion criteria: * male or female ages 6 to \< 17 years-of-age after parent or guardian's signing of informed consent. subjects with hypertension that is either: * diagnosed and untreated with a mean sitting systolic and/or diastolic blood pressure ≥ 95th percentile and ≤ 20 mm hg (systolic) and/or 10 mm hg (diastolic) above the 95th percentile at randomisation based on height-adjusted charts for age and gender; or * previously diagnosed and currently treated with mean sitting systolic blood pressure and/or diastolic blood pressure ≥ 95th percentile and ≤ 20 mm hg (systolic) and/or 10 mm hg (diastolic) above the 95th percentile at randomisation (off treatment) based on height-adjusted charts for age and gender. females of childbearing potential (post-menarche) must have a negative urine pregnancy test prior to randomization and adhere to a pregnancy prevention method (abstinence, barrier method plus spermicidal foam, oral, or implanted contraceptive). a signed informed consent by a parent or a legal guardian and an assent form signed by the subject (if applicable). exclusion criteria: * any situation, clinical condition or laboratory abnormality that, in the opinion of the investigator or sponsor, may interfere with the subject's participation in the study or would pose a significant risk to the subject or interfere with the assessment of safety and efficacy endpoints. * hypertension secondary to coarctation of the aorta, pheochromocytoma, hyperthyroidism, cushing's syndrome, or medications (eg: corticosteroids). * known history of bilateral renal artery stenosis, unilateral renal artery stenosis or a renal transplant. * glomerular filtration rate \< 50 ml/min based on an estimated value using the schwartz formula. * nephrotic syndrome not in remission. * insulin dependent diabetes mellitus. * known bleeding, coagulation, or platelet disorder that could interfere with blood sampling. * clinically significant valvular heart disease. * clinical diagnosis of heart failure. * clinically significant arrhythmia (eg, any arrhythmia requiring medical therapy or that causes symptoms). * second or third degree av block. * pregnant or breast-feeding an infant. * impaired liver function defined as either acute liver disease or chronic liver disease with persistent liver enzyme values greater than 1½ times the upper limit of the reference range for ast or alt. * known hypersensitivity to arbs. * unable to be off antihypertensive medication (diuretics, beta blockers, ace inhibitors, etc) for 6-weeks. * inability to discontinue medications which may contribute to elevated blood pressure e.g. systemic corticosteroids. * currently using, or used within 14 days prior to receiving double-blind medication, any concomitant medications which in the opinion of the investigator could negatively affect the subject. * unable or unwilling to comply with the study requirements including blood sampling and swallowing study drug tablets. * received an investigational agent within 30 days prior to receiving study medication. * alcohol or drug abuse.